The subject of laughter has been under an increasing amount of scientific scrutiny. A recent review by Dr. Sophie Scott and colleagues (Scott et al., 2014) emphasized that laughter is a social emotion. During conversations, voluntary laughter by the speaker is a communicative act. This contrasts with involuntary laughter, which is elicited by external events like jokes and funny behavior.

One basic idea about the neural systems involved in the production of laughter relies on this dual process theme:

The coordination of human laughter involves the periaqueductal grey [PAG] and the reticular formation [RF], with inputs from cortex, the basal ganglia, and the hypothalamus. The hypothalamus is more active during reactive laughter than during voluntary laughter. Motor and premotor cortices are involved in the inhibition of the brainstem laughter centres and are more active when suppressing laughter than when producing it.

An earlier paper on laughter and humor focused on neurological conditions such as pathological laughter and gelastic epilepsy (Wild et al., 2003). In gelastic epilepsy, laughter is the major symptom of a seizure. These gelastic (“laughing”) seizures usually originate from the temporal poles, the frontal poles, or from benign tumors in the hypothalamus (Wild et al., 2003). Some patients experience these seizures as pleasant (even mirthful), while others do not:

During gelastic seizures, some patients report pleasant feelings which include exhilaration or mirth. Other patients experience the attacks of laughter as inappropriate and feel no positive emotions during their laughter. It has been claimed that gelastic seizures originating in the temporal regions involve mirth but that those originating in the hypothalamus do not. This claim has been called into question, however...

In their extensive review of the literature, Wild et al. (2003) concluded that the “laughter‐coordinating centre” must lie in the dorsal midbrain, with intimate connections to PAG and RF. Together, this system may comprise the “final common pathway” for laughter (i.e., coordinating changes in facial muscles, respiration, and vocalizations). During emotional reactions, prefrontal cortex, basal temporal cortex, the hypothalamus, and the basal ganglia transmit excitatory inputs to PAG and RF, which in turn generates laughter.

Can direct cortical stimulation produce laughter and mirth?

It turns out that the basal temporal cortex (wearing a Santa hat above) plays a surprising role in the generation of mirth, at least according to a recent paper by Yamao et al., (2014). Over a period of 13 years, they recorded neural activity from the cortical surface of epilepsy patients undergoing seizure monitoring, with the purpose of localizing the aberrant epileptogenic tissue. They enrolled 13 patients with implanted subdural grids to monitor for left temporal lobe seizures, and identified induced feelings of mirth in two patients (resulting from electrical stimulation in specific regions).

Obviously, this is not the typical way we feel amusement and utter guffaws of delight, but direct stimulation of the cortical surface goes back to Wilder Penfield as a way for neurosurgeons to map the behavioral functions of the brain. Of particular interest is the localization of language-related cortex that should be spared from surgical removal if at all possible.

The mirth-inducing region (Yamao et al., 2014) encompasses what is known as the basal temporal language area (BTLA), first identified by Lüders and colleagues in 1986. The region includes the left fusiform gyrus, about 3-7 cm from the tip of the temporal lobe. Stimulation at high intensities produces total speech arrest (inability to speak) and global language comprehension problems. Low stimulation intensity produces severe anomia, an inability to name things (or places or people). Remarkably, however, Lüders et al. (1991) found that “Surgical resection of the basal temporal language area produces no lasting language deficit.”

With this background in mind, let's look at the results from the mirthful patients. The location of induced-mirth (shown below) is the white circle in Patient 1 and the black circles in Patient 2. In comparison, the locations of stimulation-induced language impairment are shown in diamonds. Note, however, that mirth was co-localized with language impairment in Patient 2.

Fig. 1 (modified from Yamao et al., 2014). The results of high-frequency electrical cortical stimulation. “Mirth” (circles) and “language” (diamonds) electrodes are shown in white and black colors for Patients 1 and 2, respectively. Note that mirth was elicited at or adjacent to the electrode associated with language impairment. R = right side. The view is of the bottom of the brain.

How do the authors interpret this finding?

...the ratio of electrodes eliciting language impairment was higher for the mirth electrodes than in no-mirth electrodes, suggesting an association between mirth and language function. Since the BTLA is actively involved in semantic processing (Shimotake et al., 2014 and Usui et al., 2003), this semantic/language area was likely involved in the semantic aspect of humor detection in our cases.

Except there was no external humor to detect, as the laughter and feelings of mirth were spontaneous. After high-frequency stimulation, one patient reported, “I do not know why, but something amused me and I laughed.” The other patient said, “A familiar melody that I had heard in a television program in my childhood came to mind; its tune sounded funny and amused me.”

The latter description sounds like memory-induced nostalgia or reminiscence, which can occur with electrical stimulation of the temporal lobe (or TL seizures). But most of the relevant stimulation sites for those déjà vu-like experiences are not in the fusiform gyrus, which has been mostly linked to higher-level visual processing.

The authors also found that stimulation of the left hippocampus consistently caused contralateral (right-sided) facial movement that led to laughter.

I might have missed it, but one thing we don't know is whether stimulation of the right fusiform gyrus would have produced similar effects. Another thing to keep in mind is that these little circles are only one part of a larger system (see Scott et al. figure above). Presumably, the stimulated BTLA sites send excitatory projections to PAG and RF, which initiate laughter. But where is mirth actually represented, if you can feel amused and laugh for no apparent reason? By bypassing higher-order regions1, laughter can be a surprising and puzzling experience.

Footnote

1 Like, IDK, maybe ventromedial PFC, other places in both frontal lobes, hypothalamus, basal ganglia, and more "classically" semantic areas in the left temporal lobe...

So it was heartening to see a team of UK researchers formally evaluate the content of 462 heath-related press releases issued by leading universities in 2011 (Sumner et al., 2014). They classified three types of exaggerated claims and found that 40% of the press releases contained exaggerated health advice, 33% made causal statements based on correlational results, and 36% extrapolated from animal research to humans.

A fine duo of exaggerated health advice and causal statements based on correlational results recently caught my eye. Here's a press release issued by Springer, the company that publishes Cognitive Therapy and Research:

When you go to bed, and how long you sleep at a time, might actually make it difficult for you to stop worrying. So say Jacob Nota and Meredith Coles of Binghamton University in the US, who found that people who sleep for shorter periods of time and go to bed very late at night are often overwhelmed with more negative thoughts than those who keep more regular sleeping hours.

The PR issues health advice (“just go to bed earlier”) based on correlational data: “people who sleep for shorter periods of time and go to bed very late at night are often overwhelmed with more negative thoughts.” But does staying up late cause you to worry, or do worries keep you awake at night? A survey can't distinguish between the two.

The study by Nota and Coles (2014) recruited 100 teenagers (or near-teenagers, mean age = 19.4 + 1.9) from the local undergraduate research pool. They filled out a number of self-report questionnaires that assessed negative affect, sleep quality, chronotype (morning person vs. evening person),1 and aspects of repetitive negative thinking (RNT).

RNT is a transdiagnostic construct that encompasses symptoms typical of depression (rumination), anxiety (worry), and obsessive-compulsive disorder (obsessions). Thus, the process of RNT is considered similar across the disorders, but the content may differ. The undergraduates were not clinically evaluated so we don't know if any of them actually had the diagnoses of depression, anxiety, and/or OCD. But one can look at whether the types of symptoms that are endorsed (whether clinically relevant or not) are related to sleep duration and timing. Which is what the authors did.

Shorter sleep duration and a later bedtime were indeed associated with more RNT. However, when accounting for levels of negative affect, the sleep variables no longer showed a significant correlation.2 Not a completely overwhelming relationship, then.

But as expected, the night owls reported more RNT than the non-night owls.

Here's how the findings were interpreted in the Springer press release and conspicuously, by the authors themselves (the study of Sumner et al., 2014 also observed this pattern). Note the exaggerated health advice and causal statements based on correlational results.

“Making sure that sleep is obtained during the right time of day may be an inexpensive and easily disseminable intervention for individuals who are bothered by intrusive thoughts,” remarks Nota.

The findings also suggest that sleep disruption may be linked to the development of repetitive negative thinking. Nota and Coles therefore believe that it might benefit people who are at risk of developing a disorder characterized by such intrusive thoughts to focus on getting enough sleep.

“If further findings support the relation between sleep timing and repetitive negative thinking, this could one day lead to a new avenue for treatment of individuals with internalizing disorders,” adds Coles. “Studying the relation between reductions in sleep duration and psychopathology has already demonstrated that focusing on sleep in the clinic also leads to reductions in symptoms of psychopathology.”

As they mentioned, we already know that many psychiatric disorders are associated with problematic sleep, and that improved sleep is helpful in these conditions. Recommending that people suffering with debilitating and uncontrollable intrusive thoughts to “just go to bed earlier” isn't particularly helpful. Not only that, such advice can be downright irritating.

Here's a news story from Yahoo that plays up the “sleep reduces worry” causal relationship even more:

Can the time you hit the hay actually influence the types of thoughts you have? Science says yes.

Are you a chronic worrier? The hour you’re going to sleep, and how much sleep you’re getting overall, may exacerbate your anxiety, according to a new study published in the journal Cognitive Therapy and Research.

The great news here? By tweaking your sleep habits you could actually help yourself worry less. Really.

Great! So internal monologues of self-loathing (“I'm a complete failure”, “No one likes me”) and deep anxiety about the future (“My career prospects are dismal”, “I worry about my partner's terrible diagnosis”) can be cured by going to bed earlier!

Even if you could forcibly alter your chronotype (and I don't know if this is possible), what do you do when you wake up in the middle of the night haunted by your repetitive negative thoughts?

1 Chronotype was dichotomously classified as evening type vs. moderately morning-type / neither type (not a lot of early birds, I guess). And only 75 students completed questionnaires in this part of the study.

2 It's notable that the significance level for these correlations was not corrected for multiple comparisons in the first place.

Monday, December 08, 2014

Hipsters are a subculture of men and women typically in their 20's and 30's that value independent thinking, counter-culture, progressive politics, an appreciation of art and indie-rock, creativity, intelligence, and witty banter. ... Hipsters reject the culturally-ignorant attitudes of mainstream consumers, and are often be seen wearing vintage and thrift store inspired fashions, tight-fitting jeans, old-school sneakers, and sometimes thick rimmed glasses.

The hipster effect is this non-concerted emergent collective phenomenon of looking alike trying to look different. Uncovering the structures behind this apparent paradox ... can have implications in deciphering collective phenomena in economics and finance, where individuals may find an interest in taking positions in opposition to the majority (for instance, selling stocks when others want to buy). Applications also extend to the case of neuronal networks with inhibition, where neurons tend to fire when others and silent, and reciprocally.

There are two kinds of people in this world: those who like to go with the flow, and those who do the opposite — hipsters, in other words. Over time, people perceive what the mainstream trend is, and either align themselves with it or oppose it.
...

What if this world contained equal numbers of conformists and hipsters? No matter how the population starts out, it will end up in some kind of cycle, as the conformists try to catch up to the hipsters, and the hipsters try to differentiate themselves from the conformists.

But there aren't equal numbers of conformists and hipsters. And this type of cycle doesn't apply to neuroscience research, which is always moving forward in terms of trends and technical advances (right)?

The BRAIN Initiative wants to train the hipsters and other "graduate students, medical students, postdoctoral scholars, medical residents, and/or early-career faculty" in Research Tools and Methods and Computational Neuroscience. This will "complement and/or enhance the training of a workforce to meet the nation’s biomedical, behavioral and clinical research needs."

Research in 2014 is a brutal business, at least for those who want to pursue academic science as a career. Perhaps the most telling line comes from the UK report: of 100 science PhD graduates, about 30 will go on to postdoc research, but just four will secure permanent academic posts with a significant research component. There are too many scientists chasing too few academic careers.

How do you respond to these brutal challenges? I don't have an answer.2But many young neuroscientists may have to start pickling their own vegetables, raising their own chickens, and curing their own meats.

Footnotes

1The average age of first-time Principal Investigators on NIH R01 grants has risen from 36 in 1980 to 42 in 2001, where it remains today (see this PPT). So this has been going on for a while.

2Or at least, not an answer that will fit within the scope of this post. Some obvious places to start are to train fewer scientists, enforce a reasonable retirement age, and increase funding somehow. And decide whether all research should be done by 20 megalabs, or else reduce the $$ amount and number of grants awarded to any one investigator.

About Me

Born in West Virginia in 1980, The Neurocritic embarked upon a roadtrip across America at the age of thirteen with his mother. She abandoned him when they reached San Francisco and The Neurocritic descended into a spiral of drug abuse and prostitution. At fifteen, The Neurocritic's psychiatrist encouraged him to start writing as a form of therapy.